Valproic acid (Depakote)

Valproic acid (Depakote) is an anti-convulsant and mood-stabilising drug, which is used to control epilepsy and bipolar disorder (manic depression). It can also be used to treat migraine and schizophrenia. Valproic acid is closely related to sodium valproate (Epilim / Convulex / Epilim Chrono) and valproate semisodium.

Valproic acid works by affecting the function of the brain chemical gamma-amino butyric acid (GABA). However, it also inhibits the activity of the enzyme histone deacetylase 1 (HDAC1), which is involved in the packaging of DNA within cells.

Side-effects include upset stomach and weight gain. More rarely, valproic acid can cause low mood, tiredness, dizziness, drowsiness, hair loss, headaches, sedation and tremor. It may also affect liver function. Due to a risk of congenital abnormalities, it should not be used during pregnancy.

Taking valproic acid with ritonavir (Norvir)-boosted protease inhibitors may lead to a reduction in valproic acid levels. Patients taking these drugs together should be monitored for a reduced effect of valproic acid. Valproic acid may also raise blood and cerebrospinal fluid levels of AZT (zidovudine, Retrovir) and blood levels of lopinavir.1 2 3 4

A small study published in August 2005 found that three of four HIV-infected patients taking valproic acid showed a 75% reduction in the amount of HIV stored within the DNA of their resting CD4 T-cells after adding the drug to antiretroviral therapy for three months.5 This is thought to be due to the drug’s effects on the HDAC1 enzyme. Although this reduction is not sufficient to release all of the HIV within cellular reservoirs, some experts thought that this may eventually point the way towards a mechanism of flushing out HIV stores and a cure for HIV infection. Additionally, early animal and preliminary human studies have also suggested that valproic acid can improve brain impairment in HIV-positive patients.6 7

Unfortunately, one study could not confirm the decline in resting CD4 T-cells.8 In 2008, two other studies confirmed that adding valproic acid to HAART does not impact the size of the HIV reservoir.9 10 11

References

  1. Antoniou T et al. Severe anemia secondary to a probable drug interaction between zidovudine and valproic acid. Clin Infect Dis 38: e38-e40, 2004
  2. Lertora JJ et al. Pharmacokinetic interaction between zidovudine and valproic acid in patients infected with human immunodeficiency virus. Clin Pharmacol Ther 56: 272-278, 1994
  3. Akula SK et al. Valproic acid increases cerebrospinal fluid zidovudine levels in a patient with AIDS. Am J Med Sci 313: 244-246, 1997
  4. di Cenzo R et al. Effects of valproic acid coadministration on plasma efavirenz and lopinavir concentrations in human immunodeficiency virus-infected adults. Antimicrob Agents Chemother 48: 4328-4331, 2004
  5. Lehrman G et al. Depletion of latent HIV-1 infection in vivo: a proof-of-concept study. Lancet 366: 549-555, 2005
  6. Dou H et al. Neuroprotective activities of sodium valproate in a murine model of human immunodeficiency virus-1 encephalitis. J Neurosci 23: 9162-9170, 2003
  7. Schifitto G et al. Valproic acid adjunctive therapy for HIV-associated cognitive impairment: a first report. Neurology 66: 919-921, 2006
  8. Siliciano JD et al. Stability of the latent reservoir for HIV-1 in patients receiving valproic acid. J Infect Dis 195: 833-836, 2007
  9. Poveda E No longer room for valproic acid as anti-HIV therapy. AIDS Rev 0(3): 190-191, 2008
  10. Sagot-Lerolle N et al. Prolonged valproic acid treatment does not reduce the size of latent HIV reservoir. AIDS 22(10): 1125-1129, 2008
  11. Achin NM et al. Valproic acid without intensified antiviral therapy has limited impact on persistent HIV infection of resting CD4+ T cells. AIDS 22(10): 1131-1136, 2008

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Community Consensus Statement on Access to HIV Treatment and its Use for Prevention

Together, we can make it happen

We can end HIV soon if people have equal access to HIV drugs as treatment and as PrEP, and have free choice over whether to take them.

Launched today, the Community Consensus Statement is a basic set of principles aimed at making sure that happens.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap
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This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends checking whether this is the most current information when making decisions that may affect your health.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member of your healthcare team for advice tailored to your situation.